Allen Kevin, Gil Mariana, Resnik Evgeny, Toader Oana, Seeburg Peter, Monyer Hannah
Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany, and Department of Molecular Neurobiology, Max Planck Institute of Medical Research, 69120 Heidelberg, Germany.
J Neurosci. 2014 Apr 30;34(18):6245-59. doi: 10.1523/JNEUROSCI.4330-13.2014.
The hippocampus and the parahippocampal region have been proposed to contribute to path integration. Mice lacking GluA1-containing AMPA receptors (GluA1(-/-) mice) were previously shown to exhibit impaired hippocampal place cell selectivity. Here we investigated whether path integration performance and the activity of grid cells of the medial entorhinal cortex (MEC) are affected in these mice. We first tested GluA1(-/-) mice on a standard food-carrying homing task and found that they were impaired in processing idiothetic cues. To corroborate these findings, we developed an L-maze task that is less complex and is performed entirely in darkness, thereby reducing numerous confounding variables when testing path integration. Also in this task, the performance of GluA1(-/-) mice was impaired. Next, we performed in vivo recordings in the MEC of GluA1(-/-) mice. MEC neurons exhibited altered grid cell spatial periodicity and reduced spatial selectivity, whereas head direction tuning and speed modulation were not affected. The firing associations between pairs of neurons in GluA1(-/-) mice were stable, both in time and space, indicating that attractor states were still present despite the lack of grid periodicity. Together, these results support the hypothesis that spatial representations in the hippocampal-entorhinal network contribute to path integration.
海马体和海马旁区域被认为有助于路径整合。先前的研究表明，缺乏含GluA1的AMPA受体的小鼠（GluA1基因敲除小鼠）表现出海马位置细胞选择性受损。在此，我们研究了这些小鼠的路径整合能力以及内嗅皮层（MEC）网格细胞的活性是否受到影响。我们首先在标准的食物携带归巢任务中测试了GluA1基因敲除小鼠，发现它们在处理自身运动线索方面存在缺陷。为了证实这些发现，我们开发了一种L型迷宫任务，该任务复杂度较低且完全在黑暗中进行，从而在测试路径整合时减少了许多混杂变量。在这个任务中，GluA1基因敲除小鼠的表现同样受损。接下来，我们在GluA1基因敲除小鼠的MEC中进行了体内记录。MEC神经元表现出网格细胞空间周期性改变和空间选择性降低，而头部方向调谐和速度调制不受影响。GluA1基因敲除小鼠中神经元对之间的放电关联在时间和空间上都是稳定的，这表明尽管缺乏网格周期性，但吸引子状态仍然存在。这些结果共同支持了海马 - 内嗅网络中的空间表征有助于路径整合的假设。
